title: Bedaquiline for the treatment of pulmonary, multidrug-resistant tuberculosis in adults.
abstract: After AIDS, tuberculosis (TB) is the leading killer worldwide due to a single infectious agent. Recently, drug-resistant strains of Mycobacterium tuberculosis elicited even more severe versions of TB. Bedaquiline inhibits mycobacterial ATP synthase. It shows potent and selective activity in vitro against M. tuberculosis, and in vivo against murine models of TB. Bedaquiline can be combined with antituberculosis and antiretroviral agents. The product displays good oral absorption, has a long terminal half-life and is metabolized mainly by cytochrome P450 3A4. In a phase II clinical trial in patients with multidrug-resistant TB, bedaquiline (combined with the standard five-drug, second-line TB regimen), showed a time to 50% culture negative conversion of 78 days, with 81.0% and 52.4% efficacy at weeks 24 and 104, respectively. Bedaquiline was generally safe and well tolerated. At the end of 2012, the U.S. Food and Drug Administration approved bedaquiline (Sirturo®) as part of a combination therapy to treat adults with multidrug-resistant TB.
authors.affiliation: jgrasescardo@hotmail.com
authors.forename: J
authors.initials: J
authors.lastname: Gras
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D064687:Diarylquinolines; D006801:Humans; D011804:Quinolines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D011804:Quinolines; C493870:bedaquiline
keywords: Anti-infective therapy; Antimycobacterial agent; Bedaquiline; MDR-TB; Proton-translocating ATP synthetase (F0F1 ATPase) inhibitors; TMC-207; Tuberculosis